Editing Glycolysis (section)

===Anoxic regeneration of NAD<sup>+</sup>===
{{Unreferenced section|date=June 2022}}
One method of doing this is to simply have the pyruvate do the oxidation; in this process, pyruvate is converted to [[lactic acid|lactate]] (the [[conjugate base]] of lactic acid) in a process called [[lactic acid fermentation]]:

:Pyruvate + NADH + H<sup>+</sup> → Lactate + NAD<sup>+</sup>

This process occurs in the [[bacterium|bacteria]] involved in making [[yogurt]] (the lactic acid causes the milk to curdle). This process also occurs in animals under hypoxic (or partially anaerobic) conditions, found, for example, in overworked muscles that are starved of oxygen. In many tissues, this is a cellular last resort for energy; most animal tissue cannot tolerate anaerobic conditions for an extended period of time.

Some organisms, such as yeast, convert NADH back to NAD<sup>+</sup> in a process called [[ethanol fermentation]].  In this process, the pyruvate is converted first to acetaldehyde and carbon dioxide, and then to ethanol.

Lactic acid fermentation and ethanol fermentation can occur in the absence of oxygen.  This anaerobic fermentation allows many single-cell organisms to use glycolysis as their only energy source.

Anoxic regeneration of NAD<sup>+</sup> is only an effective means of energy production during short, intense exercise in vertebrates, for a period ranging from 10 seconds to 2 minutes during a maximal effort in humans. (At lower exercise intensities it can sustain muscle activity in [[Mammalian diving reflex|diving animals]], such as seals, whales and other aquatic vertebrates, for very much longer periods of time.) Under these conditions NAD<sup>+</sup> is replenished by NADH donating its electrons to pyruvate to form lactate. This produces 2 ATP molecules per glucose molecule, or about 5% of glucose's energy potential (38 ATP molecules in bacteria). But the speed at which ATP is produced in this manner is about 100 times that of oxidative phosphorylation. The pH in the cytoplasm quickly drops when hydrogen ions accumulate in the muscle, eventually inhibiting the enzymes involved in glycolysis.

The burning sensation in muscles during hard exercise can be attributed to the release of hydrogen ions during the shift to glucose fermentation from glucose oxidation to carbon dioxide and water, when aerobic metabolism can no longer keep pace with the energy demands of the muscles. These hydrogen ions form a part of lactic acid. The body falls back on this less efficient but faster method of producing ATP under low oxygen conditions. This is thought to have been the primary means of energy production in earlier organisms before oxygen reached high concentrations in the atmosphere between 2000 and 2500 million years ago, and thus would represent a more ancient form of energy production than the aerobic replenishment of NAD<sup>+</sup> in cells.

The liver in mammals gets rid of this excess lactate by transforming it back into pyruvate under aerobic conditions; see [[Cori cycle]].

Fermentation of pyruvate to lactate is sometimes also called "anaerobic glycolysis", however, glycolysis ends with the production of pyruvate regardless of the presence or absence of oxygen.

In the above two examples of fermentation, NADH is oxidized by transferring two electrons to pyruvate.  However, anaerobic bacteria use a wide variety of compounds as the terminal electron acceptors in [[cellular respiration]]: nitrogenous compounds, such as nitrates and nitrites; sulfur compounds, such as sulfates, sulfites, sulfur dioxide, and elemental sulfur; carbon dioxide; iron compounds; manganese compounds; cobalt compounds; and uranium compounds.